Study objective: Evaluation of emergency department (ED) patients with chest pain who are at low risk for acute coronary syndrome is resource intensive and may lead to false-positive test results and unnecessary downstream procedures. We seek to identify patients at low short-term risk for a cardiac event for whom additional ED investigations might be unnecessary. Methods: We prospectively enrolled patients older than 24 years and with a primary complaint of chest pain from 3 academic EDs. Physicians completed standardized data collection forms before diagnostic testing. The primary adjudicated outcome was acute myocardial infarction, revascularization, or death of cardiac or unknown cause within 30 days. We used recursive partitioning to derive the rule and validated the model with 5,000 bootstrap replications. Results: Of 2,718 patients enrolled, 336 (12%) experienced a cardiac event within 30 days (6% acute myocardial infarction, 10% revascularization, 0.2% death). We developed a rule consisting of the absence of 5 predictors: ischemic ECG changes not known to be old, history of coronary artery disease, pain typical for acute coronary syndrome, initial or 6-hour troponin level greater than the 99th percentile, and age greater than 50 years. Patients aged 40 years or younger required only a single troponin evaluation. The rule was 100% sensitive (95% confidence interval 97.2% to 100.0%) and 20.9% specific (95% confidence interval 16.9% to 24.9%) for a cardiac event within 30 days. Conclusion: This clinical prediction rule identifies ED chest pain patients at very low risk for a cardiac event who may be suitable for discharge. A prospective multicenter study is needed to validate the rule and determine its effect on practice. © 2011 American College of Emergency Physicians.